Much behavioral pathology stems from dysregulation of the neural systems subserving reward. For example, impaired responsiveness to rewarding stimuli occurs in drug withdrawal and depression while there is excessive pursuit of self-destructive rewards in drug abuse and mania. In this proposal, we study three interrelated rat models of drug addiction and mood disorder by applying microarray technology to sites within the brain's reward circuits. The first and second aim are to discover gene expression correlates of the episode of diminished reward sensitivity that follows amphetamine and nicotine withdrawal, respectively. In the third aim, we determine the gene expression profile of the transition from stable to escalating self-administration of methamphetamine. It is hoped that this research will foster insight into the molecular basis of mood and substance abuse disorders as well as providing novel targets for the development of treatments for these conditions.